@article{e10f435a714c40fe8f4f8c6b05622219,
title = "Mechanisms by which autophagy regulates memory capacity in ageing",
abstract = "Autophagy agonists have been proposed to slow down neurodegeneration. Spermidine, a polyamine that acts as an autophagy agonist, is currently under clinical trial for the treatment of age-related memory decline. How Spermidine and other autophagy agonists regulate memory and synaptic plasticity is under investigation. We set up a novel mouse model of mild cognitive impairment (MCI), in which middle-aged (12-month-old) mice exhibit impaired memory capacity, lysosomes engulfed with amyloid fibrils (β-amyloid and α-synuclein) and impaired task-induced GluA1 hippocampal post-translation modifications. Subchronic treatment with Spermidine as well as the autophagy agonist TAT-Beclin 1 rescued memory capacity and GluA1 post-translational modifications by favouring the autophagy/lysosomal-mediated degradation of amyloid fibrils. These findings provide new mechanistic evidence on the therapeutic relevance of autophagy enhancers which, by improving the degradation of misfolded proteins, slow down age-related memory decline.",
keywords = "ageing, alpha-synuclein, amyloid fibrils, autophagy, GluA1, mild cognitive impairment, Spermidine",
author = "{De Risi}, Maria and Giulia Torromino and Michele Tufano and St{\'e}phanie Moriceau and Annabella Pignataro and Manon Rivagorda and Nicol{\`o} Carrano and Silvia Middei and Carmine Settembre and Martine Ammassari-Teule and Fabrizio Gardoni and Andrea Mele and Franck Oury and {De Leonibus}, Elvira",
note = "Funding Information: This work was supported by a grants from the Alzheimer's Association (NIRG-10-173992;SAGA-17-418745) to (EDL), by PRIN 2015 grants from MIUR to EDL and by Progetto Invecchiamento from MIUR (AGESPAN project from CNR to EDL), by ANR (memorautophagy) (FO); AGEMED program (FO) and FRM (EQU20190300775) (FO). The authors would like to thank Prof. Andrea Ballabio, Prof. Alessandro Treves and Prof. Antonella De Matteis for critical revision and discussion of the manuscript, Prof. Alessandro Treves for providing a criterion for mouse individual performance scoring, Dr. Laura Olivito for helping with brain sampling and Dr. Cathal Wilson for English grammar revision and critical revision of the manuscript. We thank Prof. Ana Maria Cuervo for critical discussions of the data and suggestions on the use of Spermidine as an autophagy enhancer. We are also grateful to all the other members of De Leonibus laboratory for helpful discussions and comments on this manuscript. We thank IBBC (CNR) Animal House facility and TIGEM? core facilities for supporting this work. Publisher Copyright: {\textcopyright} 2020 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2020",
month = sep,
day = "1",
doi = "10.1111/acel.13189",
language = "English",
volume = "19",
journal = "Aging Cell",
issn = "1474-9718",
publisher = "Wiley-Blackwell",
number = "9",
}